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In 2154, Klingon scientists working under the direction of Antaak recovered several Augment embryos from a hijacked Bird-of-Prey destroyed in orbit of Qu'Vat colony during the Augment Crisis. Fearing that Humans could overwhelm the Empire if they moved to staffing their ships with Augments, a project was set up to attempt to create their own Augments to counter the perceived threat.

The effort failed dreadfully. The Augments created did develop enhanced strength and intelligence, but they also began to show Human characteristics, from the blatant to the subtle. These included personality alterations and loss of the characteristic forehead ridges. Ultimately, the subjects died agonizing deaths when the incompatible DNA resulted in neural system breakdown. While working to stabilize the augmentation process, the scientific team enhanced a test subject who was, unknown to the team, also infected with Levodian flu. The flu virus in some manner incorporated the Augment DNA, turning a carefully controlled experiment into an epidemic. As the unstable augmentation process always killed the subject, this epidemic threatened the Klingon race with extinction.

The virus spread very rapidly, infecting millions within months. One of the first planets struck was N'Vak Colony. The Klingons attempted to capture DoctorArik Soong to help develop a cure, but their efforts were thwarted by Soong's incarceration in a high security detention facility. They then moved to kidnap Doctor Phlox, using Rigelian intermediaries and the assistance of Section 31 agents. Phlox was forced to work with Antaak to find a cure. However, the Klingon High Council was unwilling to wait, and dispatched a fleet to annihilate the infected planets, starting with N'Vak Colony. Afterward it set course to Qu'Vat colony. (ENT: "Affliction")

Antaak before

Antaak after

When it became clear to the research team on Qu'vat colony that it would take weeks to develop a cure, stabilizing the augment virus became the researcher's primary concern. Their efforts proved successful; a method was developed that stabilized the process in the early stages, after the cranial ridges had dissolved and some minor neural re-ordering had occurred (which caused personality changes), but before the virus became contagious, enhanced augment abilities, and caused a fatal neural pathway breakdown.

Eventually, AdmiralKrell convinced the High Council to call off their sterilization program of destroying the infected planets. The cure was distributed throughout the Empire. Because afflicted Klingons' DNA had been altered by the virus, the Human appearance and genetic traits were passed onto the descendants of the infected. Initially there were millions of Klingons who had to live with the disfigurement. (ENT: "Divergence")

A group of Klingons descended from those infected with the augment virus in 2267

In TOS: "The Savage Curtain", the Excalbians created Kahless as an affected Klingon. This may however be attributed to the fact that they created him from the minds of Humans who at that point mostly had dealings with smooth forehead Klingons.

This storyline, seen in the Star Trek: Enterprise episodes "Affliction" and "Divergence", was intended in part to explain why Original Series Klingons had a more Human appearance, and later Klingons did not. The writers also hoped the two-parter would shed some light on the change in the Klingons' temperament and disposition between the TOS and TNG eras.

In addition to the "fusion" explanation, the producers of Star Trek: Enterprise had heard many pitches, over the years, for ultimately never-produced stories aimed at explaining the change in the Klingon appearance. Additional theories included that the Klingons seen during the Original Series were from another race than those of later eras and also that some sort of disease was to blame. The Enterprise writing staff mirrored the fan community in that some felt it might be fun to account for the change, while others thought it was probably best to ignore the entire situation. The topic came up again when writer Manny Coto was named showrunner during the series' fourth season.

At first, the producers were only interested in a story with one or more "ridgeless" Klingons who had infiltrated Starfleet for the purpose of intelligence gathering. It was thought the story might involve a surgically-altered Klingon operative aboard Enterprise, someone like Arne Darvin a century later. Around this time, the writing staff had recently concluded the three-part Augment Crisis arc, and it occurred to them that some of the genetically-engineered embryos might have survived the destruction of the Bird-of-Prey, and that the Klingons might use these embryos to bio-engineer their own version of "Klingon supermen". This seemed to be a way into a story dealing with the origin of Human-like Klingons. More to the point, the Enterprise producers thought it was simply "too cool" an idea to reveal that Kor, Kang, and other Original Series Klingons may have had the DNA of Khan inside them.

While some fans clamored for an explanation for the "smooth forehead" Klingons, "Affliction" teleplay writer Mike Sussman hoped to do more – account for the apparent change in Klingon culture between the 23rd and 24th centuries. As depicted in the first Star Trek series, Klingons were notoriously savage, crafty, and at times even cowardly, putting this characterization at odds with the more noble and honorable Klingons seen in The Next Generation. The "minor neural re-ordering" noted by Phlox was intended to suggest that the augmented Klingons were not only "cursed" with a more Human appearance, but that they also inherited many Human weaknesses as well. In "Divergence", the female Laneth, newly infected by the augment virus, claimed that she "felt fear for the first time since I was a child." Her fellow augmented warriors had "become like (Humans)... weak, cowardly."

The Enterprise writers' explanation for the change in the Klingons did not – and could not – satisfy every Star Trek fan. Gene Roddenberry himself reportedly believed any "explanation" was unnecessary; the makeup seen in the films and the later series would have been too expensive during the 1960s. Roddenberry felt it was best to simply imagine that Klingons always had ridges (although this preference was officially contradicted by canon when the change was noted by the DS9 crew in "Trials and Tribble-ations").

This background information was contributed in part by former Enterprise writer/producer Mike Sussman, a member of the Memory Alpha community.

In The IDIC Epidemic, an original series novel written during the airing of The Next Generation, a Klingon scientist, Korsal, refers to the "Imperial Race," a reclusive breed of Klingons who retained their brow ridges. The Imperial Race has never been seen outside the Empire and its existence is largely a mystery to the Federation. The plague that is the subject of the novel is proven to be a mutated form of "The Imperial Plague," to which the Imperial race is very vulnerable, while smooth-headed Klingons are immune. This novel contained its own partial explanation for the difference in appearance between Klingons from the Original Series and The Next Generation - to wit, that "smooth-headed" Klingons were an offshoot of the Klingon race specifically engineered or selected for contact with outside forces.

In "Against Their Nature", the first installment of the IDW ComicsStar Trek: Klingons - Blood Will Tell series, it is suggested that, while Phlox's cure removed Augment strength and Augment intelligence, those affected did retain Augment ambition, and as such they were largely responsible for the expansion of the Klingon Empire between Enterprise and TOS, and were able to take control of the High Council.

In the novel Forged in Fire, it is revealed that the virus did not solely affect Klingons; the ridged Trill witnessed in "The Host" – as opposed to the spotted Trill seen in Star Trek: Deep Space Nine and later episodes – are the result of a strain of the augment virus that managed to infect a Trill colony through visiting Klingon traders. However, the Trill seemed not to be interested in working on methods of restoring the original Trill look, with this "sub-group" having recently (at the time the novel was set) being re-accepted back into Trill society. The novel also reveals that the appearance of The Albino – who is not only Klingon but is in fact Kor's cousin – was an unintended side-effect of prenatal genetic engineering intended to cure his bloodline of the virus.